1. Field of the Invention
The invention relates to multiple branch peptide constructions (MBPCs) and to their use in the treatment of Human Immunodeficiency Virus (HIV) infections.
2. Background of the Invention
The use of radially branched systems in polymers has been known for a long time in classical polymer chemistry. This system has been used by J. P. Tam [Proc. Natl. Acad. Sci. USA 85, 5409-5413 (1988)] to develop antigens without the use of ambiguous carriers, using lysine skeletons. Those antigens were designed to generate vaccines against a variety of diseases. Antigens for generating vaccines against HIV infection are described by Tam in WO93/03766. He called them Multiple Antigenic Peptide Systems (MAPS), consistent with their conceived use.
The present inventors, along with others, found that similar constructions with shorter peptides derived from the V3 loop of the surface envelope glycoprotein gp120 of HIV offered a direct therapeutic approach to the treatment of HIV infections, as described in WO95/07929. The name MAPS was then inappropriate, and the compounds were renamed as MBPCs. The MBPCs of WO95/07929 interfered with the virus envelope—cell membrane fusion step and also the infected cell membrane—uninfected cell membrane fusion step, either step being thought to be indispensable for cell infection, virus multiplication and the spread of virus in the host organism, by blockading the CD4 receptor present in cells such as lymphocytes and macrophages, apparently by attaching to a membrane co-receptor which is distinct from the CD4 binding receptor, without causing the cell to lose its ability to be activated by other antigens or mitogens.